In today's obesogenic environment many individuals struggle to regulate caloric intake, which leads to obesity and associated comorbidities (e.g., hypertension, diabetes). The exposure to endogenous (e.g., gustatory cues) and exogenous (e.g., environmental food-paired cues) signals associated with meal intake can, through learning, influence both the regulation and dysregulation of appetite control. As obesity rates continue to rise, there is a critical need to develop effective strategies to combat this epidemic. This includes the elucidation of neurobiological and psychological variables underlying the learned effects that influence eating behaviors. To this end, I propose that the lateral hypothalamus (LH) feeding signal Melanin Concentrating Hormone (MCH) acts as a modulator of predictive regulation and gates associations between anticipatory food cues and reward signals. In doing so, I anticipate that LH MCH neurons will modulate the regulation of blood glucose, and the disruption to appetite control that follows either exposure to intense artificial sweeteners, or environmental cues associated with food. Thus, the proposed research will significantly advance understanding of the psychobiological variables that contribute to: metabolic regulation, weight gain, obesity and metabolic disorders (e.g., diabetes). In the proposed research, I will combine DREADD and optogenetic techniques with sophisticated behavioral and ingestive learning approaches in mice to address two specific aims. In Aim 1, I will examine LH MCH modulation over cephalic responding and the detrimental influences over glucoregulation that occur following prolonged artificial sweetener consumption. In Aim 2, I will examine the psychological mechanisms and neurobiological circuitry underlying LH MCH modulation of overeating in response to environmental food-paired cues.